# Antimicrobial resistance genes and antibiotic use in chronic lung disease: a bronchoscopy study of the lower airways microbiome

## TL;DR

This study found higher levels of antibiotic resistance genes in the lungs of patients with chronic lung diseases compared to healthy individuals, especially in sarcoidosis and IPF, and linked these to recent antibiotic use.

## Contribution

The study provides the first detailed comparison of antimicrobial resistance genes in the lower airways of patients with chronic lung diseases versus healthy controls.

## Key findings

- Patients with sarcoidosis and IPF had significantly higher presence of ARGs compared to controls.
- ARG counts were significantly higher in individuals who had used antibiotics within the past three months.
- Tetracycline resistance was the most common type of ARG found in the lower airways.

## Abstract

Antimicrobial resistance genes (ARGs) in the respiratory microbiome are poorly characterised. We compared the presence of ARGs in healthy controls with patients with chronic lung disease in a cross-sectional study, adjusted for time since antibiotic use.

Bronchoalveolar lavage was collected from 100 controls, and 93 patients with chronic obstructive pulmonary disease (COPD), 13 with asthma, 34 with sarcoidosis, 12 with idiopathic pulmonary fibrosis (IPF) and 11 patients with unclassifiable interstitial lung disease (uILD). Participants had not used antibiotics 14 days prior to sampling. Shotgun metagenomic sequencing was performed with Illumina NovaSeq. ARGs were identified using the National Database of Antibiotic-Resistant Organisms. Sample reads were normalised to counts per million.

In total, 38% of controls had at least one ARG, compared with 51%, 39%, 65% and 83% of patients with COPD, asthma, sarcoidosis and IPF, respectively (p=0.01). ARGs against tetracycline (33%) were the most common ARG class, followed by beta-lactam and macrolide resistance (both 26%). In a logistic regression analysis adjusted for sex, age, body composition, smoking and antibiotic use, the OR (95% CI) for having ARGs in the lower airways was 1.30 (0.70 to 2.41) in COPD, 1.00 (0.29 to 3.52) in asthma, 3.52 (1.40 to 8.83) in sarcoidosis, 6.40 (1.25 to 32.73) in IPF and 3.27 (0.76 to 14.16) in uILD compared with controls. Overall mean (SD) ARG counts per million were 403.8 (537.7) in the 35 subjects who had used antibiotics ≤3 months before bronchoscopy, compared with 197.6 (355.9) in the 228 subjects without (p=0.02).

The presence of ARGs in the lower airways microbiome was significantly higher in patients with sarcoidosis and IPF than in controls. The counts per million for ARGs were significantly associated with recent antibiotic use.